UH3 Project: Pragmatic Trial of Higher vs. Lower Serum Phosphate Targets in Patients Undergoing Hemodialysis (HiLo)
Overview
Principal Investigator:
Sponsoring Institution: Duke University
Collaborators:
- DaVita, Inc.
NIH Institute Providing Oversight: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Program Official: Susan Mendley, MD (NIDDK)
Project Scientist: Kevin Chan, MD (NIDDK)
ClinicalTrials.gov Identifier: NCT04095039
Trial Status: Enrolling
Trial Summary
As the population ages and therapeutic advances improve life expectancies of chronic diseases, the prevalence of end-stage renal disease (ESRD) inexorably increases. Kidney transplantation is the preferred treatment, but an insufficient organ supply renders dialysis the only treatment option for most patients. Although dialysis outcomes have improved modestly in recent years, annual rates of hospitalizations and mortality remain unacceptably high and quality of life is poor. Starved for therapeutic advances to improve outcomes, the nephrology community has adopted opinion-based clinical practice guidelines for many aspects of ESRD care, including management of phosphate. Current guidelines advocate aggressive treatment of hyperphosphatemia to near normal levels (~5.0 mg/dl) using dietary phosphate binders and highly restrictive diets; however, because there have been no randomized clinical outcomes trials, the assumed benefits of this approach are unproven, potential harms have not been identified, and the optimal serum phosphate target is unknown. To address this important unmet need, we are conducting “HiLo”, a large, randomized pragmatic trial to be conducted as one of the NIH Collaboratory Trials of the NIH Health Care Systems Research Collaboratory. HiLo is evaluating the effects on all-cause survival and hospitalization of liberalizing serum phosphate target to >6.5 mg/dl versus the current standard approach of targeting phosphate levels to <5.5 mg/dl among patients undergoing maintenance hemodialysis. The trial will enroll 4400 patients and will be fully embedded in the clinical care delivery of >100 dialysis facilities owned and operated by a large, national dialysis provider organization. The HiLo Data Coordinating Center is based at the Duke Clinical Research Institute (DCRI), a highly experienced academic research organization and the Coordinating Center for the Collaboratory. The project is being implemented in two phases – a UG3 planning phase and a UH3 implementation phase – each of which has specific milestones. In addition to addressing a question of high clinical relevance in ESRD, HiLo will advance the field of pragmatic trials through several innovations: 1) answering a pressing clinical question rather than evaluating strategies to enhance implementation of a proven therapy; 2) using a novel electronic approach for patient-level consent to enable pragmatic evaluation of a “more than minimal risk” intervention for the first time in ESRD; and 3) providing a precedent for a novel hierarchical composite endpoint in ESRD trials. Given the importance of the trial question to patients, clinicians, dialysis providers, and payers, and the “real-world” approach to testing the intervention, the findings of HiLo will be rapidly implemented and readily sustained upon completion of the trial. Additionally, and importantly, HiLo will pave the way for future pragmatic trials in ESRD and more broadly.
Data and Resource Sharing
- HiLo-2019-UH3 Follow-up
HiLo-Ethics and Regulatory UH3 Follow-up
- HiLo Ethics and Regulatory Discussion
HiLo Ethics and Regulatory Discussion
Featured Interviews
Dr. Wolf discusses the HiLo NIH Collaboratory Trial, a Pragmatic Trial of Higher vs. Lower Serum Phosphate Targets in Patients Undergoing Hemodialysis.
News and Interviews
- News_A Year of New Insights From the NIH Collaboratory
December 14, 2021: A Year of New Insights From the NIH Collaboratory
- News_A Year of Results and New Insights From the NIH Collaboratory
December 15, 2020: A Year of Results and New Insights From the NIH Collaboratory
- News_HiLo_Implementation
October 7, 2020: A Year Into Implementation, HiLo Shares an Update and Lessons Learned
- News_HiLo Awarded Continuation From Planning to Implementation Phase
September 13, 2019: HiLo Awarded Continuation From Planning to Implementation Phase
- News_Spotlight on a New Demonstration Project_HiLo
September 7, 2018: Spotlight on a New NIH Collaboratory Trial: HiLo
- Video Interview with Dr. Myles Wolf
Video Interview: Interview with Dr. Myles Wolf, Principal Investigator of HiLo
Publications
- Richesson et al J Am Med Inform Assoc 2021
Enhancing the use of EHR systems for pragmatic embedded research: lessons from the NIH Health Care Systems Research Collaboratory
- Edmonston et al Am J Kidney Dis 2020
HiLo Study Design Paper
- Musgrove and Wolf Annu Rev Physiol 2020
Regulation and effects of FGF23 in chronic kidney disease
- Living Textbook Chapter_Which PCTs Should Have a DMC
Living Textbook Chapter: Which PCTs Should Have a DMC?
- Living Textbook_The Embedded Pragmatic Trials Ecosystem
Living Textbook: The Embedded Pragmatic Clinical Trial Ecosystem
- HiLo Study Snapshot
HiLo Study Snapshot
Presentations
- SC-Mtg-2023-Day1-Chakraborty
Hrishikesh Chakraborty Presentation at 2023 Steering Committee Meeting
- 2022 NIH Workshop_Wolf
2022 NIH Workshop HiLo Presentation
- SC-Mtg-2022-Day-2-Wolf
HiLo Presentation at 2022 Steering Committee Meeting
- GR-Video-10-09-20
Pragmatic Trial of Higher vs. Lower Serum Phosphate Targets in Patients Undergoing Hemodialysis (HiLo) (GR Video 2020)
- GR-Slides-10-09-20
Pragmatic Trial of Higher vs. Lower Serum Phosphate Targets in Patients Undergoing Hemodialysis (HiLo) (GR Slides 2020)
- SC-2019-UG3-HiLo
UG3 Updates at the 2019 SC Meeting-HiLo
- Workshop on the Design and Analysis of PCTs_Panel 4_Unique Considerations
Workshop on the Design and Analysis of PCTs: Panel 4: Unique Considerations
- GR-Video-01-18-19
Pragmatic Trials in End-stage Renal Disease (ESRD): HiLo (GR Video 2019)
- GR-Slides-01-18-19
Pragmatic Trials in End-stage Renal Disease (ESRD): HiLo (GR Slides 2019)
- 4.-Wolf_The-HiLo-Trial_15-min_FINAL
The HiLo Trial Update
- 13. Wolf_The HiLo Trial_5 min_FINAL
The HiLo Trial Overview